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2017 ; 19
(6
): 635-642
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Causes of death in Prader-Willi syndrome: Prader-Willi Syndrome Association (USA)
40-year mortality survey
#MMPMID27854358
Butler MG
; Manzardo AM
; Heinemann J
; Loker C
; Loker J
Genet Med
2017[Jun]; 19
(6
): 635-642
PMID27854358
show ga
BACKGROUND: Prader-Willi syndrome (PWS) is a rare, complex, neurodevelopmental
genetic disorder that is associated with hyperphagia and morbid obesity in humans
and leads to a shortened life expectancy. This report summarizes the primary
causes of death and evaluates mortality trends in a large cohort of individuals
with PWS. METHODS: The US Prader-Willi Syndrome Association (PWSA (USA))
syndrome-specific database of death reports was collected through a cursory
bereavement program for PWSA (USA) families using a brief survey created in 1999.
Causes of death were descriptively characterized and statistically examined using
Cox proportional hazards. RESULTS: A total of 486 deaths were reported (263
males, 217 females, 6 unknown) between 1973 and 2015, with mean age of 29.5?±?16
years (2 months-67 years); 70% occurred in adulthood. Respiratory failure was the
most common cause, accounting for 31% of all deaths. Males were at increased risk
for presumed hyperphagia-related accidents/injuries and cardiopulmonary factors
compared to females. PWS maternal disomy 15 genetic subtype showed an increased
risk of death from cardiopulmonary factors compared to the deletion subtype.
CONCLUSIONS: These findings highlight the heightened vulnerability to obesity and
hyperphagia-related mortality in PWS. Future research is needed to address
critical vulnerabilities such as gender and genetic subtype in the cause of death
in PWS.Genet Med advance online publication 17 November 2016.